The primary aim of this proposal is to study plasma levels of gamma-aminobutyric acid (GABA) in normal control subjects and in patients with primary affective disorder. Several preliminary studies, supported in part by an NIMH Mental Health Small grant, suggest that plasma GABA levels are low in patients with unipolar depression when compared to control. Patients with bipolar affective disorder had levels of plasma GABA that were in the control range when depressed, but plasma GABA levels that were elevated above control when the patients were manic and after they had experienced a clinical recovery. This work needs to be continued and extended. First, a larger group of normal controls will be studied to determine the stability of plasma GABA over time. Second, a series of medication-free patients with primary unipolar depression, bipolar depression, and mania will have their plasma GABA levels determined while they are ill and symptomatic. Plasma GABA will again be obtained in the patients after they have recovered from the episode and are asymptomatic and can safely be withdrawn from medication. This research should contribute to our understanding of the role GABA plays in the pathophysiology of affective disorder.